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Opioid analgesics remain widely used for pain treatment despite the related serious side effects. Some of those, such as opioid tolerance and opioid-induced hyperalgesia may be at least partially due to modulation of opioid receptors (OR) function at nociceptive synapses in the spinal cord dorsal horn. It was suggested that increased release of different chemokines under pathological conditions may play a role in this process. The goal of this study was to investigate the crosstalk between the µOR, transient receptor potential vanilloid 1 (TRPV1) receptor and C-C motif ligand 2 (CCL2) chemokine and the involvement of spinal microglia in the modulation of opioid analgesia.
Learn More >Background The Centers for Disease Control and Prevention (CDC) issued guidelines and certain healthcare payers have made pharmacy coverage changes (PCC) focusing on regulating prescription opioids. Aim We evaluated differences in the rate of first-time opioid fills at doses ≥ 50 morphine milligram equivalents (MME)/day and first-time opioid fills with benzodiazepine fill overlap following the CDC guidelines and following a PCC between provider types, geographic locations, and insurance types. Method We used OptumLabs® Data Warehouse claims data between 2014 and 2018. Subjects were opioid naïve non-cancer care patients, 18 years and older who had an identified chronic pain condition ICD diagnosis within 2 weeks prior to their first-time opioid fill. We used multiple treatment period segmented regression analysis with interaction terms to test the differences between primary care providers (PCPs) and specialist providers (SPs), urban and rural primary care service areas (PCSAs), and Medicare Advantage (MA) and commercially insured patients (CIPs) in their first-time opioid fill patterns. Results Prescribing first-time opioid fills at doses ≥ 50MME/day declined following the CDC guidelines and PCC, the decline was greater among SPs than PCPs and in rural PCSAs than urban PCSAs. Also, following the CDC guidelines, the decline was greater among MA patients however following the PCC the decline was greater among CIPs. There were no differences in rate of first-time opioid fill with benzodiazepine overlap between groups. Conclusion Responses to the CDC opioid guidelines and a PCC differed between PCPs and SPs, urban and rural PCSAs, and when prescribing to MA and CIPs. Understanding these differences is important to help inform future guidelines.
Learn More >Implanted spinal neuromodulation (SNMD) techniques are used in the treatment of refractory chronic pain. They involve the implantation of electrodes around the spinal cord (spinal cord stimulation (SCS)) or dorsal root ganglion (dorsal root ganglion stimulation (DRGS)), and a pulse generator unit under the skin. Electrical stimulation is then used with the aim of reducing pain intensity.
Learn More >Chronic pain, pain catastrophizing, and mental health disorders such as anxiety or depression frequently occur together and are challenging to treat. To help understand the relationship between these conditions, we sought to identify distinct phenotypes associated with worse pain and function. In a cohort of people with chronic pain on opioids seeking medical cannabis in New York, we conducted latent class analysis to identify clusters of participants based on pain catastrophizing and mental health symptoms of depression, anxiety, post-traumatic stress disorder (PTSD) and attention deficit/hyperactivity disorder (ADHD). We then compared clusters with respect to sociodemographic and clinical characteristics using descriptive statistics. Among 185 participants, we identified four discrete groups: low pain catastrophizing and low mental health symptoms (49% of participants), low pain catastrophizing and ADHD-predominant mental health symptoms (11%), high pain catastrophizing and anxiety-predominant mental health symptoms (11%), and high pain catastrophizing and high mental health symptoms (30%). The group with high pain catastrophizing and high mental health symptoms had the worst pain intensity and interference, disability, insomnia, and quality of life, compared to the two groups with lower pain catastrophizing, though not all differences were statistically significant. Our findings highlight the importance of identifying and addressing pain catastrophizing in patients with comorbid chronic pain and mental health symptoms.
Learn More >This study aimed to explore the independent risk factors for postherpetic neuralgia (PHN).
Learn More >Antagonists of the P2X7 receptor (P2X7R) have the potential to treat diseases where neuroinflammation is present such as depression, chronic pain and Alzheimer's disease. We recently developed a structural hybrid (C1; 1-((adamantan-1-yl)methyl)-2-cyano-3-(quinolin-5-yl)guanidine) of a purported competitive P2X7R antagonist (C2; 2-cyano-1-((1S)-1-phenylethyl)-3-(quinolin-5-yl)guanidine) and a likely negative allosteric modulator (NAM) of the P2X7R (C3; N-((adamantan-1-yl)methyl)-2-chloro-5-methoxybenzamide). Here we aimed to pharmacologically characterize C1, to gain insights into how select structural components impact antagonist interaction with the P2X7R. A second aim was to examine the role of the peptide LL-37, an apparent activator of the P2X7R, and compare the ability of multiple P2X7R antagonists to block its effects. Compounds 1, 2 and 3 were characterised using washout, Schild and receptor protection studies, all using dye uptake assays in HEK293 cells expressing the P2X7R. LL-37 was examined in the same HEK293 cells and THP-1 monocytes. Compounds 2 and 3 acted as a BzATP-competitive antagonist and NAM of the P2X7R respectively. Compound 1 was a slowly reversible NAM of the P2X7R suggesting the incorporation of an appropriately positioned adamantane promotes binding to the allosteric site of the P2X7R. LL-37 was shown to potentiate the ability of ATP to induce dye uptake at low concentrations (1-3 μg mL) or induce dye uptake alone at higher concentrations (10-20 μg mL). None of the P2X7R antagonists studied were able to block LL-37-induced dye uptake bringing in to question the ability of current P2X7R antagonists to inhibit the inflammatory action of LL-37 in vivo.
Learn More >In recent years, the issue of postoperative pain has raised wide concern in the medical community. Postoperative hyperalgesia (POH), as the primary etiology of pain, has been extensively studied and numerous articles have been published on this topic; however, no comprehensive bibliometric review of POH publications has been conducted. Thus, we aimed to examine the 100 top-cited reports on POH and summarize their key characteristics.
Learn More >Few treatments exist for acute attacks of trigeminal neuralgia. Therefore, this study aimed to investigate the efficacy and safety of an intravenous fosphenytoin therapy protocol in a trigeminal neuralgia crisis. We conducted a single-center, retrospective, observational study of the records of 20 patients with trigeminal neuralgia who received intravenous fosphenytoin therapy (15 mg/mL in normal saline at 50 mg/min for 15 min, total 750 mg) during hospitalization between September 2015 and August 2020. Serum phenytoin concentration was measured 30 min post-infusion. Pain severity was evaluated using a numerical rating scale and was analyzed for statistical significance. The mean age of the patients was 67.5 years (female, 50.0%). The median numerical rating scale score (interquartile range) of pain severity was 2.35 (0-10), 0.65 (0-5), 0.15 (0-1), 2.00 (0-8), and 4.30 (0-10) at 15, 30, and 60 min, and 12 and 24 h, respectively (p < .001); the numerical rating scale score was 10 before treatment. Reduction in pain 24 h following treatment was significant. The mean phenytoin concentration was 12.8 μg/mL 30 min post-treatment. While mild dizziness occurred in four patients, all could walk independently within 60 min. The mean age and weight of patients with mild dizziness were significantly higher and lower, respectively (p < .001), than those of other patients. These results may provide physicians with new insights into the innovative therapeutic option of intravenous fosphenytoin and contribute to advancements in treating acute trigeminal neuralgia crisis.
Learn More >The current study was designed to test the hypothesis that BmK AGAP (AGAP) potentiates the analgesic effect of lidocaine. The chronic constrictive injury was performed on 72 rats to induce a rapid onset and long-lasting pain. The rats were randomly assigned to one of six groups; Group A (n = 12) received an intrathecal administration of saline, Group B (n = 12) received an intrathecal injection of lidocaine, Group C (n = 12) received an intrathecal administration of AGAP, Group D, E, and F (n = 12 each) received an intrathecal administration of lidocaine 0.005 mg/ml + AGAP 25, 50, 100 μg/kg respectively. The von Frey filaments were used to assess mechanical allodynia. Nav1.7 and TRPV1 currents were recorded by the whole-cell aspiration patch-clamp technique, and KCNQ2/3 currents were recorded by the whole-cell drilling patch-clamp technique. The whole-cell aspiration patch-clamp technique showed that AGAP inhibited TRPV1and KCNQ2/3 currents and increased the analgesic effect of lidocaine. AGAP may have a synergistic effect with lidocaine which demonstrates a potential therapeutic approach for optimizing post-operative analgesia.
Learn More >There is an enormous need for pain education among all health care professions before and after licensure. The study goal was to explore generic and chronic pain-specific factors that influenced uptake of a continuous education program for chronic pain, the Project Extension for Community Health Outcomes (ECHO) CHUM Douleur chronique.
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